Autism, fever, epigenetics and the locus coeruleus

Mark F. Mehler, Dominick P. Purpura

Research output: Contribution to journalReview articlepeer-review

89 Scopus citations


Some children with autism spectrum disorders (ASD) exhibit improved behaviors and enhanced communication during febrile episodes. We hypothesize that febrigenesis and the behavioral-state changes associated with fever in autism depend upon selective normalization of key components of a functionally impaired locus coeruleus-noradrenergic (LC-NA) system. We posit that autistic behaviors result from developmental dysregulation of LC-NA system specification and neural network deployment and modulation linked to the core behavioral features of autism. Fever transiently restores the modulatory functions of the LC-NA system and ameliorates autistic behaviors. Fever-induced reversibility of autism suggests preserved functional integrity of widespread neural networks subserving the LC-NA system and specifically the subsystems involved in mediating the cognitive and behavioral repertoires compromised in ASD. Alterations of complex gene-environmental interactions and associated epigenetic mechanisms during seminal developmental critical periods are viewed as instrumental in LC-NA dysregulation as emphasized by the timing and severity of prenatal maternal stressors on autism prevalence. Our hypothesis has implications for a rational approach to further interrogate the interdisciplinary etiology of ASD and for designing novel biological detection systems and therapeutic agents that target the LC-NA system's diverse network of pre- and postsynaptic receptors, intracellular signaling pathways and dynamic epigenetic remodeling processes involved in their regulation and functional plasticity.

Original languageEnglish (US)
Pages (from-to)388-392
Number of pages5
JournalBrain Research Reviews
Issue number2
StatePublished - Mar 2009


  • Developmental critical period
  • Gene-environmental interaction
  • Homeostatic signal
  • Imprinted gene
  • Neuromodulator
  • Pharmacoepigenomic agent
  • Prenatal stressor
  • Sensorimotor processing

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology


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